Thyroid neoplasms

Thyroid neoplasmsDr ramakrishna PG(ENT)

Classification Two lobes anterolateral to the larynx and trachea.Isthmuscovered anteriorly by the infrahyoid (or strap muscles)Blood supplyinternal jugular lymph nodes (levels 3 and 4) as well as para-tracheal and pretracheal nodes.

Table 335-9 Classification of Thyroid Neoplasms

Benign Follicular epithelial cell adenomas Macrofollicular (colloid) Normofollicular (simple) Microfollicular (fetal) Trabecular (embryonal) Hrtle cell variant (oncocytic) MalignantApproximate Prevalence, %Follicular epithelial cell Well-differentiated carcinomas Papillary carcinomas 8090 Pure papillary Follicular variant Diffuse sclerosing variant Tall cell, columnar cell variants Follicular carcinomas 510 Minimally invasive Widely invasive Hrthle cell carcinoma (oncocytic) Insular carcinoma Undifferentiated (anaplastic) carcinomas C cell (calcitonin-producing) 10 Medullary thyroid cancer Sporadic Familial MEN 2 Other malignancies Lymphomas 12 Sarcomas Metastases Others

Thyroid lymphomabackground of Hashimoto's thyroiditis. A rapidly expanding thyroid mass Diffuse large-cell lymphoma is the most common Biopsies reveal sheets of lymphoid cells that can be difficult to distinguish from small-cell lung cancer highly sensitive to external radiation. Surgical resection should be avoided as initial therapy because it may spread disease that is otherwise localized to the thyroid

Anaplastic carcinomapoorly differentiated and aggressive cancer. The prognosis is poor, and most patients die within 6 months of diagnosis. Because of the undifferentiated state of these tumors, the uptake of radioiodine is usually negligible, but it can be used therapeutically if there is residual uptake.anthracyclines and paclitaxel, -ineffective. External beam radiation therapy can be attempted and continued if tumors are responsive

MTC sporadic or familial accounts for about 510% of thyroid cancers. There are three familial forms of MTC: MEN 2A, MEN 2B, and familial MTC without other features of MEN . In general, MTC is more aggressive in MEN 2B than in MEN 2A, and familial MTC is more aggressive than sporadic MTC. Elevated serum calcitonin provides a marker of residual or recurrent disease to test all patients with MTC for RET mutations, as genetic counseling and testing of family members can be offered to those individuals who test positive for mutations. surgical. these tumors do not take up radioiodine. External radiation treatment and chemotherapy may provide palliation in patients with advanced disease

Neoplastic Thyroid DiseaseThyroid Nodules GoiterMultinodularDiffuseEndemicThyroid CancerWell differentiated and poorly differentiated

Thyroid Nodular DiseaseThyroid gland nodules are common in the general population Palpable nodules occur in approximately 5% of the US population, mainly in womenMost thyroid nodules are benign Less than 5% are malignantOnly 8% to 10% of patients with thyroid nodules have thyroid cancer

13Thyroid Nodular Disease.Thyroid nodules are the most common endocrine disorder.1,2 Although thyroid nodules commonly occur and their presence raises questions about malignancy, fewer than 5% are found to be malignant3 and only 8%-10% of patients with thyroid nodules have thyroid cancer.2 The prevalence of thyroid nodules is about 4%-7% in iodine-sufficient areas and much higher in iodine-deficient countries.2,4 Thyroid nodular disease is very common in the US, with palpable nodules occurring in approximately 5% of adults, especially women.5 The frequency of thyroid nodular disease increases throughout adult life.2 Nodules can be detected in an otherwise normal gland, but are especially prevalent in iodine-deficient areas in the form of multiple nodules in an enlarged thyroid gland (multinodular goiter).1 Toxic uninodular or multinodular goiter accounts for 10% to 40% of cases of hyperthyroidism and is more common in older patients.2 Thyroid nodules can be divided into 2 types: "hot" or autonomously functioning thyroid nodules (AFTN), and nonfunctioning or "cold" thyroid nodules (CTN).6 AFTN are characterized by nonautoimmune hyperthyroidism and nodular proliferation. CTN are without function and are less differentiated.6 A defect in the expression or structure of the NIS gene is thought to cause impaired iodide trapping in nonfunctioning CTN.1

References Tonacchera M, et al. J Clin Endocrinol Metab. 2002;87:352-357.2. Hardman JG, Limbird LE, eds. Goodman and Gilmans The Pharmacological Basis of Therapeutics, 9th ed. New York, NY: McGraw Hill;1996:1396.3. Bennedbaek FN, et al. J Clin Endocrinol Metab. 2000;85:2493-2498.4. Tonacchera M, et al. J Clin Endocrinol Metab. 1999;84:4155-4158.5. Singer PA. Otolaryngol Clin North Am. 1996; 29:577-591.6. Eszlinger M, et al. J Clin Endocrinol Metab. 2001;86:4834-4842

Multinodular Goiter (MNG)MNG is an enlarged thyroid gland containing multiple nodulesThe thyroid gland becomes more nodular with increasing ageIn MNG, nodules typically vary in sizeMost MNGs are asymptomaticMNG may be toxic or nontoxicToxic MNG occurs when multiple sites of autonomous nodule hyperfunction develop, resulting in thyrotoxicosisToxic MNG is more common in the elderly

14Multinodular Goiter (MNG).The thyroid gland becomes more nodular with age.1 MNG develops in an enlarged thyroid gland and is especially prevalent in populations in iodine-deficient areas.2 Thyroid enlargement may have progressed from a simple nontoxic goiter or have been associated with Hashimoto disease.3 MNG usually results from a low-grade, probably intermittent stimulus to the thyroid gland from iodine deficiency, goitrogens (foods that induce hypothyroidism and goiter in the diet such as cabbage, broccoli, cauliflower, and brussels sprouts),4 decreased thyroid hormone production, or an autoimmune disease, which causes multiplication and growth of small groups of thyroid cells.3 After Graves disease, toxic multinodular goiter (TMG) is the most common cause of hyperthyroidism5 and thyrotoxicosis in the elderly.6 TMG occurs most often in patients aged 50 or older and mainly in women, when the nodules in a nontoxic MNG become autonomous5 and function independent of TSH stimulation.7 It is very prevalent in geographic regions with iodine deficiency and rarely occurs in places where iodine intake is sufficient. Thyroid autonomy is most frequently found in TMGs.7 Patients are often asymptomatic or very mildly toxic, and have a goiter, and lab findings that indicate suppressed TSH with normal FT4 and T3 levels.5References1. Hurley DL, et al. Geriatrics. 1995;50:24-26,29-31.2. Tonacchera M, et al. J Clin Endocrinol Metab. 2002;87:352-367.3. Bayliss RIS, Tunbridge WMG. Thyroid Disease: the Facts. 3rd ed. Oxford, UK: Oxford University Press; 1998:121.4. Stoewsand GS. Food Chem Toxicol. 1995;33:537-543.5. Fisher JN. South Med J. 2002;95:493-505.6. Vitti P, et al. J Endocrinol Invest. 2002;25(10 Suppl):16-18.7. Krohn K, et al. J Clin Endocrinol Metab. 2001;86:3336-3345.

Endemic Goiter serious health concern in parts of the world with iodine deficiency including mountainous areas or areas with high rainfall/flooding

Kaplan, E. et al. Thyroid Disease Manager Surgery of the Thyroid Gland Chapter 21, May 99

Thyroid CarcinomaIncidenceThyroid carcinoma occurs relatively infrequently compared to the common occurrence of benign thyroid diseaseThyroid cancers account for only 0.74% of cancers among men, and 2.3% of cancers in women in the USThe annual rate has increased nearly 50% since 1973 to approximately 18 000 casesThyroid carcinomas (percentage of all US cases)Papillary (80%)Follicular (about 10%)Medullary thyroid (5%-10%)Anaplastic carcinoma (1%-2%)Primary thyroid lymphomas (rare)Metastatic from other primary sites (rare)

16Thyroid Carcinoma.The annual rate of thyroid cancer in the United States has risen nearly 50% since 1973, striking approximately 18 000 people.1 Thyroid cancers account for about 90% of newly diagnosed endocrine malignancies and cause about 1200 deaths each year.1,2 Thyroid carcinoma is 3 times more common in women than in men.3 Thyroid cancer mortality rates fell significantly (20%) in the US between 1973 and 1996, most likely because of early diagnosis and effective treatment of the common forms of thyroid cancer.1 The decline in mortality was seen only in women, possibly because they undergo routine medical examinations more frequently than men.1 Thyroid cancers comprise 4 carcinoma and 2 miscellaneous types (percentage of thyroid neoplasms in the US): papillary (80%), follicular (about 10%), medullary (5%-10%), and anaplastic carcinomas (1%- 2%); plus primary thyroid lymphoma and sarcoma (rare).3 Anaplastic thyroid carcinomas are invasive and almost always fatal.2 Papillary and follicular thyroid cancers are referred to as differentiated thyroid cancer (DTC), which is usually curable when discovered at an early stage.1 DTC comprises 90% of thyroid cancers and 70% of thyroid cancer deaths.1 A known cause of thyroid carcinoma is low-dose radiation exposure.4 The risk is increased in women, who have a 40% higher rate of radiation-induced thyroid cancer than men, and if radiation exposure occurs before15 years of age.4 Ninety percent of radiation-induced thyroid cancers are papillary thyroid carcinoma; the remaining 9%-10% are follicular carcinomas. Anaplastic or medullary carcinomas are rare.4References1. Mazzaferri E, et al. J Clin Endocrinol Metab. 2001;86:1447-1463.2. Heaney AT, et al. J Clin Endocrinol Metab. 2001;86:5025-5032.3. Sharma PK, Johns MM. Thyroid cancer. [eMedicine Specialties Web site]. September 14, 2001. Available at http://www.emedicine.com/ent/topic646.htm. Accessed July 2, 2003. 4. Yeung S-CJ. Endocr Rev. 1998;19:144-172.

Initial Evaluation of a Thyroid Nodule/Mass

17

Risk factors for MalignancySolitary thyroid nodules in patients >60 or 3 or 4 cm)Growth of nodule

Evaluating Thyroid NodulesTSH measurementUltrasound of the thyroidFine needle aspirationRadioactive iodine imaging

Kim N, et al. Otolaryngol Clin North Am. 2003;36:17-33.Braverman LE, Utiger RD, eds. Werner & Ingbars The Thyroid: A Fundamental and Clinical Text. 8th ed. Philadelphia, Pa: Lippincott, Williams & Wilkins; 2000.Castro MR, et al. Endocr Pract. 2003;9:128-136.

19Evaluating Thyroid Nodules.Evaluation of a thyroid nodule begins with an assessment of the underlying function of the thyroid with a TSH measurement.1 A low TSH level suggests a hyperfunctioning nodule, which is unlikely to be malignant and can be diagnosed readily with RAI scanning.1 If TSH is elevated, levothyroxine sodium (LT4) therapy is used to return the TSH to normal levels before additional evaluation of the nodule.2 In many cases with elevated TSH, the palpable nodule is indicative of Hashimotos thyroiditis, and it resolves after several weeks of LT4 therapy.2 Nodules that persist after adequate LT4 replacement therapy for several weeks should be re-evaluated.Following the functional assessment, a structural assessment of the thyroid should be done by physical examination and thyroid ultrasound.1 The thyroid ultrasound provides valuable information on the location and size of the thyroid nodule.1After the nodule is localized in the thyroid, fine needle aspiration (FNA) is the most cost-effective method for distinguishing between benign and malignant nodules.1 Because only 5% of all nodules are malignant, most FNA tests will identify benign nodules.3 Approximately 5% of FNA samples will be frankly malignant.2 Approximately 10% of FNAs have an adequate cell sample, but cytological features of the thyroid cells are not sufficient for differentiating between benign and malignant nodules, particularly in follicular lesions in which the cellular architecture of benign follicular cells and FTC are very similar.3 These lesions can only be differentiated on the basis of vascular or capsular invasion and therefore require surgical removal and careful histological evaluation of the nodule. Occasionally, an FNA will not yield an adequate thyroid follicular cell sample for evaluation, and these samples are deemed inadequate to make a definitive diagnosis.3 Usually, the FNA is repeated in order to obtain an adequate number of thyroid cells for evaluation.3References1. Kim N, et al. Otolaryngol Clin North Am. 2003;36:17-33.2. Braverman LE, Utiger RD, eds. Werner & Ingbars The Thyroid: A Fundamental and Clinical Text. 8th ed. Philadelphia, Pa: Lippincott, Williams & Wilkins; 2000.3. Castro MR, et al. Endocr Pract. 2003;9:128-136.

Thyroid Ultrasonography

20Evaluating Thyroid Nodules.Evaluation of a thyroid nodule begins with an assessment of the underlying function of the thyroid with a TSH measurement.1 A low TSH level suggests a hyperfunctioning nodule, which is unlikely to be malignant and can be diagnosed readily with RAI scanning.1 If TSH is elevated, levothyroxine sodium (LT4) therapy is used to return the TSH to normal levels before additional evaluation of the nodule.2 In many cases with elevated TSH, the palpable nodule is indicative of Hashimotos thyroiditis, and it resolves after several weeks of LT4 therapy.2 Nodules that persist after adequate LT4 replacement therapy for several weeks should be re-evaluated.Following the functional assessment, a structural assessment of the thyroid should be done by physical examination and thyroid ultrasound.1 The thyroid ultrasound provides valuable information on the location and size of the thyroid nodule.1After the nodule is localized in the thyroid, fine needle aspiration (FNA) is the most cost-effective method for distinguishing between benign and malignant nodules.1 Because only 5% of all nodules are malignant, most FNA tests will identify benign nodules.3 Approximately 5% of FNA samples will be frankly malignant.2 Approximately 10% of FNAs have an adequate cell sample, but cytological features of the thyroid cells are not sufficient for differentiating between benign and malignant nodules, particularly in follicular lesions in which the cellular architecture of benign follicular cells and FTC are very similar.3 These lesions can only be differentiated on the basis of vascular or capsular invasion and therefore require surgical removal and careful histological evaluation of the nodule. Occasionally, an FNA will not yield an adequate thyroid follicular cell sample for evaluation, and these samples are deemed inadequate to make a definitive diagnosis.3 Usually, the FNA is repeated in order to obtain an adequate number of thyroid cells for evaluation.3References1. Kim N, et al. Otolaryngol Clin North Am. 2003;36:17-33.2. Braverman LE, Utiger RD, eds. Werner & Ingbars The Thyroid: A Fundamental and Clinical Text. 8th ed. Philadelphia, Pa: Lippincott, Williams & Wilkins; 2000.3. Castro MR, et al. Endocr Pract. 2003;9:128-136.

Thyroid UltrasonographyExcellent for characterizing size and other features of noduleUseful in localizing nodule for FNACannot distinguish between benign vs. malignant

21Evaluating Thyroid Nodules.Evaluation of a thyroid nodule begins with an assessment of the underlying function of the thyroid with a TSH measurement.1 A low TSH level suggests a hyperfunctioning nodule, which is unlikely to be malignant and can be diagnosed readily with RAI scanning.1 If TSH is elevated, levothyroxine sodium (LT4) therapy is used to return the TSH to normal levels before additional evaluation of the nodule.2 In many cases with elevated TSH, the palpable nodule is indicative of Hashimotos thyroiditis, and it resolves after several weeks of LT4 therapy.2 Nodules that persist after adequate LT4 replacement therapy for several weeks should be re-evaluated.Following the functional assessment, a structural assessment of the thyroid should be done by physical examination and thyroid ultrasound.1 The thyroid ultrasound provides valuable information on the location and size of the thyroid nodule.1After the nodule is localized in the thyroid, fine needle aspiration (FNA) is the most cost-effective method for distinguishing between benign and malignant nodules.1 Because only 5% of all nodules are malignant, most FNA tests will identify benign nodules.3 Approximately 5% of FNA samples will be frankly malignant.2 Approximately 10% of FNAs have an adequate cell sample, but cytological features of the thyroid cells are not sufficient for differentiating between benign and malignant nodules, particularly in follicular lesions in which the cellular architecture of benign follicular cells and FTC are very similar.3 These lesions can only be differentiated on the basis of vascular or capsular invasion and therefore require surgical removal and careful histological evaluation of the nodule. Occasionally, an FNA will not yield an adequate thyroid follicular cell sample for evaluation, and these samples are deemed inadequate to make a definitive diagnosis.3 Usually, the FNA is repeated in order to obtain an adequate number of thyroid cells for evaluation.3References1. Kim N, et al. Otolaryngol Clin North Am. 2003;36:17-33.2. Braverman LE, Utiger RD, eds. Werner & Ingbars The Thyroid: A Fundamental and Clinical Text. 8th ed. Philadelphia, Pa: Lippincott, Williams & Wilkins; 2000.3. Castro MR, et al. Endocr Pract. 2003;9:128-136.

Thyroid UltrasonographyCertain features may suggest greater risk of cancer:Irregular or poorly defined borders of noduleLack of a "haloHypo-echogenicityEvidence of microcalcificationsIncreased blood flowGrowth and interval change on serial ultrasounds

22Evaluating Thyroid Nodules.Evaluation of a thyroid nodule begins with an assessment of the underlying function of the thyroid with a TSH measurement.1 A low TSH level suggests a hyperfunctioning nodule, which is unlikely to be malignant and can be diagnosed readily with RAI scanning.1 If TSH is elevated, levothyroxine sodium (LT4) therapy is used to return the TSH to normal levels before additional evaluation of the nodule.2 In many cases with elevated TSH, the palpable nodule is indicative of Hashimotos thyroiditis, and it resolves after several weeks of LT4 therapy.2 Nodules that persist after adequate LT4 replacement therapy for several weeks should be re-evaluated.Following the functional assessment, a structural assessment of the thyroid should be done by physical examination and thyroid ultrasound.1 The thyroid ultrasound provides valuable information on the location and size of the thyroid nodule.1After the nodule is localized in the thyroid, fine needle aspiration (FNA) is the most cost-effective method for distinguishing between benign and malignant nodules.1 Because only 5% of all nodules are malignant, most FNA tests will identify benign nodules.3 Approximately 5% of FNA samples will be frankly malignant.2 Approximately 10% of FNAs have an adequate cell sample, but cytological features of the thyroid cells are not sufficient for differentiating between benign and malignant nodules, particularly in follicular lesions in which the cellular architecture of benign follicular cells and FTC are very similar.3 These lesions can only be differentiated on the basis of vascular or capsular invasion and therefore require surgical removal and careful histological evaluation of the nodule. Occasionally, an FNA will not yield an adequate thyroid follicular cell sample for evaluation, and these samples are deemed inadequate to make a definitive diagnosis.3 Usually, the FNA is repeated in order to obtain an adequate number of thyroid cells for evaluation.3References1. Kim N, et al. Otolaryngol Clin North Am. 2003;36:17-33.2. Braverman LE, Utiger RD, eds. Werner & Ingbars The Thyroid: A Fundamental and Clinical Text. 8th ed. Philadelphia, Pa: Lippincott, Williams & Wilkins; 2000.3. Castro MR, et al. Endocr Pract. 2003;9:128-136.

RAI imagingFormerly had been used extensively in the initial work up of nodular thyroid diseaseFNA is now considered the gold standard

RAI imagingThe problem:Although hot nodules are usually never cancer, only 5% of all nodules are hyperfunctioningThe remaining 90-95% that are warm or cold could be cancer and thus require FNA

RAI imagingCircumstances where RAI imaging may be useful and indicated:Suppressed TSH (more likely to have a autonomously functioning nodule)Multiple nodules, none dominantOther

25Evaluating Thyroid Nodules.Evaluation of a thyroid nodule begins with an assessment of the underlying function of the thyroid with a TSH measurement.1 A low TSH level suggests a hyperfunctioning nodule, which is unlikely to be malignant and can be diagnosed readily with RAI scanning.1 If TSH is elevated, levothyroxine sodium (LT4) therapy is used to return the TSH to normal levels before additional evaluation of the nodule.2 In many cases with elevated TSH, the palpable nodule is indicative of Hashimotos thyroiditis, and it resolves after several weeks of LT4 therapy.2 Nodules that persist after adequate LT4 replacement therapy for several weeks should be re-evaluated.Following the functional assessment, a structural assessment of the thyroid should be done by physical examination and thyroid ultrasound.1 The thyroid ultrasound provides valuable information on the location and size of the thyroid nodule.1After the nodule is localized in the thyroid, fine needle aspiration (FNA) is the most cost-effective method for distinguishing between benign and malignant nodules.1 Because only 5% of all nodules are malignant, most FNA tests will identify benign nodules.3 Approximately 5% of FNA samples will be frankly malignant.2 Approximately 10% of FNAs have an adequate cell sample, but cytological features of the thyroid cells are not sufficient for differentiating between benign and malignant nodules, particularly in follicular lesions in which the cellular architecture of benign follicular cells and FTC are very similar.3 These lesions can only be differentiated on the basis of vascular or capsular invasion and therefore require surgical removal and careful histological evaluation of the nodule. Occasionally, an FNA will not yield an adequate thyroid follicular cell sample for evaluation, and these samples are deemed inadequate to make a definitive diagnosis.3 Usually, the FNA is repeated in order to obtain an adequate number of thyroid cells for evaluation.3References1. Kim N, et al. Otolaryngol Clin North Am. 2003;36:17-33.2. Braverman LE, Utiger RD, eds. Werner & Ingbars The Thyroid: A Fundamental and Clinical Text. 8th ed. Philadelphia, Pa: Lippincott, Williams & Wilkins; 2000.3. Castro MR, et al. Endocr Pract. 2003;9:128-136.

Thyroid FNANow considered the most cost effective and sensitive/specific diagnostic test of thyroid nodulesThe use of US has expanded the role of FNA in evaluating nodules and improved the validity of the results

Thyroid FNAPossible FNA ResultsBenign: 70 -75 % Malignant: Up to 5% Suspicious: About 10% Nondiagnostic: About 10 - 20%

Thyroid FNALimitationsFalse negatives: (< 5% of FNA) more likely in large (>4cm) or small (4cm) or small nodules (3.0) who also have + thyroid autoantibodies (controversial)

Thyroid Carcinoma

37

Typical Presentation of Thyroid CancerPainless lumpNormal thyroid function testsFound on routine examination or by the patientSlow growth or no growth over several monthsKim N, et al. Otolaryngol Clin North Am. 2003;36:17-33.Thyroid Disease Manager Web site. Available at: http://www.thyroidmanager.org. Accessed December 10, 2003.Mazzaferri EL, et al. J Clin Endocrinol Metab. 2001;86:1447-1463.

38Typical Presentation of Thyroid Cancer.Most thyroid cancers present in clinically euthyroid patients who have normal thyroid function tests. These tests, including those measuring thyroid stimulating hormone (TSH), thyroxine (T4), and triiodothyronine (T3), are measurements of the functional status of the thyroid and provide no information on the presence or absence of structural disease of the thyroid (eg, nodules).1 A mass in the thyroid may be found during a routine examination by a health care provider or may be noted by the patient.1 Often thyroid cancer is present in a nodule for months or years with only minimal growth.2 Thus, lack of consistent nodule size over long periods of time does not rule out the presence of thyroid cancer.3

References1. Kim N, et al. Otolaryngol Clin North Am. 2003;36:17-33.2. Thyroid Disease Manager Web site. Available at: http://www.thyroidmanager.org. Accessed December 10, 2003.3. Mazzaferri EL, et al. J Clin Endocrinol Metab. 2001;86:1447-1463.

Newly Diagnosed Cancer in the United States

050100150200250Thyroid Cancer 22 000 new cases1400 deathsCancer facts and figures. American Cancer Society Web site. Available at: http://www.cancer.org/downloads/STT/CAFF2003PWSecured.pdf. Accessed December 10, 2003.New Cases, Thousands

39Newly Diagnosed Cancer in the United States.Although the incidence of thyroid cancer is not as high as that of lung, breast, or prostate cancer, the number of thyroid cases diagnosed annually is comparable to the number of cases of multiple myeloma, kidney cancer, and leukemia diagnosed each year.1In 2003, an estimated 22 000 new cases of thyroid cancer will be diagnosed and an estimated 1400 patients will die of thyroid cancer.1

Reference1. Cancer facts and figures. American Cancer Society Web site. Available at: http://www.cancer.org/downloads/STT/CAFF2003PWSecured.pdf. Accessed December 10, 2003.

Types of Thyroid CancerPapillary (80%-85%): develops from thyroid follicle cells in 1 or both lobes; grows slowly but can spreadFollicular (5%-10%): common in countries with insufficient iodine consumption; lymph node metastases are uncommonMedullary: develops from C-cells, can spread quickly; sporadic and familial typesAnaplastic: develops from existing papillary or follicular cancers; aggressive, usually fatalLymphoma: develops from lymphocytes; uncommonDetailed guide: thyroid cancer. American Cancer Society Web site. Available at: http://www.cancer.org/docroot/CRI/CRI_2_3x.asp?dt=43. Accessed December 10, 2003.

40Types of Thyroid Cancer.Thyroid cancer is more common in women than in men, and occurs most frequently in individuals between 35 and 45 years of age. There are several types of thyroid cancer.1 Papillary thyroid cancer (PTC) is the most common form, comprising 80% to 85% of thyroid cancers. Papillary thyroid cancer and follicular thyroid cancer (FTC) arise from thyroid follicle cells. Papillary thyroid cancer is frequently a multifocal and bilateral disease while follicular thyroid cancer tends to present as a single focus within the thyroid gland.2 Papillary cancers grow slowly, but often spread to regional cervical lymph nodes.Follicular thyroid cancer accounts for approximately 5% to 10% of thyroid cancers.1 It is more common in countries where the population does not have sufficient iodine intake.1 Follicular cancer infrequently spreads to regional cervical nodes, but can spread to the lungs and bones.1 Medullary thyroid cancer (MTC) develops from the C-cells and can spread quickly to the lymph nodes, lungs, or liver before a thyroid nodule is detected.1 Medullary cancer can either be sporadic or can arise as a part of a number of genetic syndromes associated with endocrine abnormalities, including hyperparathyroidism and pheochromocytoma (such as multiple endocrine neoplasia [MEN] 2 syndrome).1Anaplastic thyroid cancer (ATC) is uncommon, and is believed to develop from existing papillary or follicular carcinomas.1 Anaplastic thyroid cancer is one of the most aggressive and lethal of all solid malignancies. In most series, 3-year survival rates were less than 10%.3 Thyroid lymphoma is a rare disease that usually arises in the setting of pre-existing chronic lymphocytic thyroiditis (Hashimotos thyroiditis).2

References1. Detailed guide: thyroid cancer. American Cancer Society Web site. Available at: http://www.cancer.org/docroot/CRI/CRI_2_3x.asp?dt=43. Accessed December 10, 2003.2. Braverman LE, Utiger RD, eds. Werner & Ingbars The Thyroid: A Fundamental and Clinical Text. 8th ed. Philadelphia, Pa: Lippincott, Williams & Wilkins; 2000.3. Types of thyroid cancer. Virginia Masen Medical Center Web site. Available at: http://www.vmmc.org/dbCancer/sec180604.htm. Accessed December 10, 2003.

Papillary Thyroid CancerMost common typeMakes up about 80% of all thyroid carcinomas in the United StatesFemales outnumber males 3:1Highest incidence in women in midlife

Detailed guide: thyroid cancer. American Cancer Society Web site. Available at: http://www.cancer.org/docroot/CRI/CRI_2_3x.asp?dt=43. Accessed December 10, 2003.Thyroid Disease Manager Web site. Available at: http://www.thyroidmanager.org. Accessed December 10, 2003.

41Papillary Thyroid Cancer. Papillary thyroid cancer is the most common type of thyroid cancer and accounts for approximately 80% to 85% of all diagnosed thyroid cancers in the United States.1Papillary thyroid cancer has a 3-fold higher incidence in women than in men, and has a peak incidence in the third and fourth decades of life.2Approximately two thirds of PTC is found to have follicular elements and is often classified histologically as a follicular variant of papillary thyroid carcinoma.2

References1. Detailed guide: thyroid cancer. American Cancer Society Web site. Available at: http://www.cancer.org/docroot/CRI/CRI_2_3x.asp?dt=43. Accessed December 10, 2003.2. Thyroid Disease Manager Web site. Available at: http://www.thyroidmanager.org. Accessed December 10, 2003.

Papillary Thyroid CancerCharacteristicsUnencapsulated tumor nodule with ill-defined marginsTumor typically firm and solidMay present as nodal enlargementCommonly metastasizes to neck and mediastinal lymph nodes40% to 60% in adults and 90% in children60 or 3 or 4 cm)Growth of nodule

Evaluating Thyroid NodulesTSH measurementUltrasound of the thyroidFine needle aspirationRadioactive iodine imaging

Kim N, et al. Otolaryngol Clin North Am. 2003;36:17-33.Braverman LE, Utiger RD, eds. Werner & Ingbars The Thyroid: A Fundamental and Clinical Text. 8th ed. Philadelphia, Pa: Lippincott, Williams & Wilkins; 2000.Castro MR, et al. Endocr Pract. 2003;9:128-136.

51Evaluating Thyroid Nodules.Evaluation of a thyroid nodule begins with an assessment of the underlying function of the thyroid with a TSH measurement.1 A low TSH level suggests a hyperfunctioning nodule, which is unlikely to be malignant and can be diagnosed readily with RAI scanning.1 If TSH is elevated, levothyroxine sodium (LT4) therapy is used to return the TSH to normal levels before additional evaluation of the nodule.2 In many cases with elevated TSH, the palpable nodule is indicative of Hashimotos thyroiditis, and it resolves after several weeks of LT4 therapy.2 Nodules that persist after adequate LT4 replacement therapy for several weeks should be re-evaluated.Following the functional assessment, a structural assessment of the thyroid should be done by physical examination and thyroid ultrasound.1 The thyroid ultrasound provides valuable information on the location and size of the thyroid nodule.1After the nodule is localized in the thyroid, fine needle aspiration (FNA) is the most cost-effective method for distinguishing between benign and malignant nodules.1 Because only 5% of all nodules are malignant, most FNA tests will identify benign nodules.3 Approximately 5% of FNA samples will be frankly malignant.2 Approximately 10% of FNAs have an adequate cell sample, but cytological features of the thyroid cells are not sufficient for differentiating between benign and malignant nodules, particularly in follicular lesions in which the cellular architecture of benign follicular cells and FTC are very similar.3 These lesions can only be differentiated on the basis of vascular or capsular invasion and therefore require surgical removal and careful histological evaluation of the nodule. Occasionally, an FNA will not yield an adequate thyroid follicular cell sample for evaluation, and these samples are deemed inadequate to make a definitive diagnosis.3 Usually, the FNA is repeated in order to obtain an adequate number of thyroid cells for evaluation.3References1. Kim N, et al. Otolaryngol Clin North Am. 2003;36:17-33.2. Braverman LE, Utiger RD, eds. Werner & Ingbars The Thyroid: A Fundamental and Clinical Text. 8th ed. Philadelphia, Pa: Lippincott, Williams & Wilkins; 2000.3. Castro MR, et al. Endocr Pract. 2003;9:128-136.

Thyroid Ultrasonography

52Evaluating Thyroid Nodules.Evaluation of a thyroid nodule begins with an assessment of the underlying function of the thyroid with a TSH measurement.1 A low TSH level suggests a hyperfunctioning nodule, which is unlikely to be malignant and can be diagnosed readily with RAI scanning.1 If TSH is elevated, levothyroxine sodium (LT4) therapy is used to return the TSH to normal levels before additional evaluation of the nodule.2 In many cases with elevated TSH, the palpable nodule is indicative of Hashimotos thyroiditis, and it resolves after several weeks of LT4 therapy.2 Nodules that persist after adequate LT4 replacement therapy for several weeks should be re-evaluated.Following the functional assessment, a structural assessment of the thyroid should be done by physical examination and thyroid ultrasound.1 The thyroid ultrasound provides valuable information on the location and size of the thyroid nodule.1After the nodule is localized in the thyroid, fine needle aspiration (FNA) is the most cost-effective method for distinguishing between benign and malignant nodules.1 Because only 5% of all nodules are malignant, most FNA tests will identify benign nodules.3 Approximately 5% of FNA samples will be frankly malignant.2 Approximately 10% of FNAs have an adequate cell sample, but cytological features of the thyroid cells are not sufficient for differentiating between benign and malignant nodules, particularly in follicular lesions in which the cellular architecture of benign follicular cells and FTC are very similar.3 These lesions can only be differentiated on the basis of vascular or capsular invasion and therefore require surgical removal and careful histological evaluation of the nodule. Occasionally, an FNA will not yield an adequate thyroid follicular cell sample for evaluation, and these samples are deemed inadequate to make a definitive diagnosis.3 Usually, the FNA is repeated in order to obtain an adequate number of thyroid cells for evaluation.3References1. Kim N, et al. Otolaryngol Clin North Am. 2003;36:17-33.2. Braverman LE, Utiger RD, eds. Werner & Ingbars The Thyroid: A Fundamental and Clinical Text. 8th ed. Philadelphia, Pa: Lippincott, Williams & Wilkins; 2000.3. Castro MR, et al. Endocr Pract. 2003;9:128-136.

Thyroid UltrasonographyExcellent for characterizing size and other features of noduleUseful in localizing nodule for FNACannot distinguish between benign vs. malignant

53Evaluating Thyroid Nodules.Evaluation of a thyroid nodule begins with an assessment of the underlying function of the thyroid with a TSH measurement.1 A low TSH level suggests a hyperfunctioning nodule, which is unlikely to be malignant and can be diagnosed readily with RAI scanning.1 If TSH is elevated, levothyroxine sodium (LT4) therapy is used to return the TSH to normal levels before additional evaluation of the nodule.2 In many cases with elevated TSH, the palpable nodule is indicative of Hashimotos thyroiditis, and it resolves after several weeks of LT4 therapy.2 Nodules that persist after adequate LT4 replacement therapy for several weeks should be re-evaluated.Following the functional assessment, a structural assessment of the thyroid should be done by physical examination and thyroid ultrasound.1 The thyroid ultrasound provides valuable information on the location and size of the thyroid nodule.1After the nodule is localized in the thyroid, fine needle aspiration (FNA) is the most cost-effective method for distinguishing between benign and malignant nodules.1 Because only 5% of all nodules are malignant, most FNA tests will identify benign nodules.3 Approximately 5% of FNA samples will be frankly malignant.2 Approximately 10% of FNAs have an adequate cell sample, but cytological features of the thyroid cells are not sufficient for differentiating between benign and malignant nodules, particularly in follicular lesions in which the cellular architecture of benign follicular cells and FTC are very similar.3 These lesions can only be differentiated on the basis of vascular or capsular invasion and therefore require surgical removal and careful histological evaluation of the nodule. Occasionally, an FNA will not yield an adequate thyroid follicular cell sample for evaluation, and these samples are deemed inadequate to make a definitive diagnosis.3 Usually, the FNA is repeated in order to obtain an adequate number of thyroid cells for evaluation.3References1. Kim N, et al. Otolaryngol Clin North Am. 2003;36:17-33.2. Braverman LE, Utiger RD, eds. Werner & Ingbars The Thyroid: A Fundamental and Clinical Text. 8th ed. Philadelphia, Pa: Lippincott, Williams & Wilkins; 2000.3. Castro MR, et al. Endocr Pract. 2003;9:128-136.

Thyroid UltrasonographyCertain features may suggest greater risk of cancer:Irregular or poorly defined borders of noduleLack of a "haloHypo-echogenicityEvidence of microcalcificationsIncreased blood flowGrowth and interval change on serial ultrasounds

54Evaluating Thyroid Nodules.Evaluation of a thyroid nodule begins with an assessment of the underlying function of the thyroid with a TSH measurement.1 A low TSH level suggests a hyperfunctioning nodule, which is unlikely to be malignant and can be diagnosed readily with RAI scanning.1 If TSH is elevated, levothyroxine sodium (LT4) therapy is used to return the TSH to normal levels before additional evaluation of the nodule.2 In many cases with elevated TSH, the palpable nodule is indicative of Hashimotos thyroiditis, and it resolves after several weeks of LT4 therapy.2 Nodules that persist after adequate LT4 replacement therapy for several weeks should be re-evaluated.Following the functional assessment, a structural assessment of the thyroid should be done by physical examination and thyroid ultrasound.1 The thyroid ultrasound provides valuable information on the location and size of the thyroid nodule.1After the nodule is localized in the thyroid, fine needle aspiration (FNA) is the most cost-effective method for distinguishing between benign and malignant nodules.1 Because only 5% of all nodules are malignant, most FNA tests will identify benign nodules.3 Approximately 5% of FNA samples will be frankly malignant.2 Approximately 10% of FNAs have an adequate cell sample, but cytological features of the thyroid cells are not sufficient for differentiating between benign and malignant nodules, particularly in follicular lesions in which the cellular architecture of benign follicular cells and FTC are very similar.3 These lesions can only be differentiated on the basis of vascular or capsular invasion and therefore require surgical removal and careful histological evaluation of the nodule. Occasionally, an FNA will not yield an adequate thyroid follicular cell sample for evaluation, and these samples are deemed inadequate to make a definitive diagnosis.3 Usually, the FNA is repeated in order to obtain an adequate number of thyroid cells for evaluation.3References1. Kim N, et al. Otolaryngol Clin North Am. 2003;36:17-33.2. Braverman LE, Utiger RD, eds. Werner & Ingbars The Thyroid: A Fundamental and Clinical Text. 8th ed. Philadelphia, Pa: Lippincott, Williams & Wilkins; 2000.3. Castro MR, et al. Endocr Pract. 2003;9:128-136.

RAI imagingFormerly had been used extensively in the initial work up of nodular thyroid diseaseFNA is now considered the gold standard

RAI imagingThe problem:Although hot nodules are usually never cancer, only 5% of all nodules are hyperfunctioningThe remaining 90-95% that are warm or cold could be cancer and thus require FNA

RAI imagingCircumstances where RAI imaging may be useful and indicated:Suppressed TSH (more likely to have a autonomously functioning nodule)Multiple nodules, none dominantOther

57Evaluating Thyroid Nodules.Evaluation of a thyroid nodule begins with an assessment of the underlying function of the thyroid with a TSH measurement.1 A low TSH level suggests a hyperfunctioning nodule, which is unlikely to be malignant and can be diagnosed readily with RAI scanning.1 If TSH is elevated, levothyroxine sodium (LT4) therapy is used to return the TSH to normal levels before additional evaluation of the nodule.2 In many cases with elevated TSH, the palpable nodule is indicative of Hashimotos thyroiditis, and it resolves after several weeks of LT4 therapy.2 Nodules that persist after adequate LT4 replacement therapy for several weeks should be re-evaluated.Following the functional assessment, a structural assessment of the thyroid should be done by physical examination and thyroid ultrasound.1 The thyroid ultrasound provides valuable information on the location and size of the thyroid nodule.1After the nodule is localized in the thyroid, fine needle aspiration (FNA) is the most cost-effective method for distinguishing between benign and malignant nodules.1 Because only 5% of all nodules are malignant, most FNA tests will identify benign nodules.3 Approximately 5% of FNA samples will be frankly malignant.2 Approximately 10% of FNAs have an adequate cell sample, but cytological features of the thyroid cells are not sufficient for differentiating between benign and malignant nodules, particularly in follicular lesions in which the cellular architecture of benign follicular cells and FTC are very similar.3 These lesions can only be differentiated on the basis of vascular or capsular invasion and therefore require surgical removal and careful histological evaluation of the nodule. Occasionally, an FNA will not yield an adequate thyroid follicular cell sample for evaluation, and these samples are deemed inadequate to make a definitive diagnosis.3 Usually, the FNA is repeated in order to obtain an adequate number of thyroid cells for evaluation.3References1. Kim N, et al. Otolaryngol Clin North Am. 2003;36:17-33.2. Braverman LE, Utiger RD, eds. Werner & Ingbars The Thyroid: A Fundamental and Clinical Text. 8th ed. Philadelphia, Pa: Lippincott, Williams & Wilkins; 2000.3. Castro MR, et al. Endocr Pract. 2003;9:128-136.

Thyroid FNANow considered the most cost effective and sensitive/specific diagnostic test of thyroid nodulesThe use of US has expanded the role of FNA in evaluating nodules and improved the validity of the results

Thyroid FNAPossible FNA ResultsBenign: 70 -75 % Malignant: Up to 5% Suspicious: About 10% Nondiagnostic: About 10 - 20%

Thyroid FNALimitationsFalse negatives: (< 5% of FNA) more likely in large (>4cm) or small (4cm) or small nodules (3.0) who also have + thyroid autoantibodies (controversial)

Thyroid Carcinoma

69

Typical Presentation of Thyroid CancerPainless lumpNormal thyroid function testsFound on routine examination or by the patientSlow growth or no growth over several monthsKim N, et al. Otolaryngol Clin North Am. 2003;36:17-33.Thyroid Disease Manager Web site. Available at: http://www.thyroidmanager.org. Accessed December 10, 2003.Mazzaferri EL, et al. J Clin Endocrinol Metab. 2001;86:1447-1463.

70Typical Presentation of Thyroid Cancer.Most thyroid cancers present in clinically euthyroid patients who have normal thyroid function tests. These tests, including those measuring thyroid stimulating hormone (TSH), thyroxine (T4), and triiodothyronine (T3), are measurements of the functional status of the thyroid and provide no information on the presence or absence of structural disease of the thyroid (eg, nodules).1 A mass in the thyroid may be found during a routine examination by a health care provider or may be noted by the patient.1 Often thyroid cancer is present in a nodule for months or years with only minimal growth.2 Thus, lack of consistent nodule size over long periods of time does not rule out the presence of thyroid cancer.3

References1. Kim N, et al. Otolaryngol Clin North Am. 2003;36:17-33.2. Thyroid Disease Manager Web site. Available at: http://www.thyroidmanager.org. Accessed December 10, 2003.3. Mazzaferri EL, et al. J Clin Endocrinol Metab. 2001;86:1447-1463.

Newly Diagnosed Cancer in the United States

050100150200250Thyroid Cancer 22 000 new cases1400 deathsCancer facts and figures. American Cancer Society Web site. Available at: http://www.cancer.org/downloads/STT/CAFF2003PWSecured.pdf. Accessed December 10, 2003.New Cases, Thousands

71Newly Diagnosed Cancer in the United States.Although the incidence of thyroid cancer is not as high as that of lung, breast, or prostate cancer, the number of thyroid cases diagnosed annually is comparable to the number of cases of multiple myeloma, kidney cancer, and leukemia diagnosed each year.1In 2003, an estimated 22 000 new cases of thyroid cancer will be diagnosed and an estimated 1400 patients will die of thyroid cancer.1

Reference1. Cancer facts and figures. American Cancer Society Web site. Available at: http://www.cancer.org/downloads/STT/CAFF2003PWSecured.pdf. Accessed December 10, 2003.

Types of Thyroid CancerPapillary (80%-85%): develops from thyroid follicle cells in 1 or both lobes; grows slowly but can spreadFollicular (5%-10%): common in countries with insufficient iodine consumption; lymph node metastases are uncommonMedullary: develops from C-cells, can spread quickly; sporadic and familial typesAnaplastic: develops from existing papillary or follicular cancers; aggressive, usually fatalLymphoma: develops from lymphocytes; uncommonDetailed guide: thyroid cancer. American Cancer Society Web site. Available at: http://www.cancer.org/docroot/CRI/CRI_2_3x.asp?dt=43. Accessed December 10, 2003.

72Types of Thyroid Cancer.Thyroid cancer is more common in women than in men, and occurs most frequently in individuals between 35 and 45 years of age. There are several types of thyroid cancer.1 Papillary thyroid cancer (PTC) is the most common form, comprising 80% to 85% of thyroid cancers. Papillary thyroid cancer and follicular thyroid cancer (FTC) arise from thyroid follicle cells. Papillary thyroid cancer is frequently a multifocal and bilateral disease while follicular thyroid cancer tends to present as a single focus within the thyroid gland.2 Papillary cancers grow slowly, but often spread to regional cervical lymph nodes.Follicular thyroid cancer accounts for approximately 5% to 10% of thyroid cancers.1 It is more common in countries where the population does not have sufficient iodine intake.1 Follicular cancer infrequently spreads to regional cervical nodes, but can spread to the lungs and bones.1 Medullary thyroid cancer (MTC) develops from the C-cells and can spread quickly to the lymph nodes, lungs, or liver before a thyroid nodule is detected.1 Medullary cancer can either be sporadic or can arise as a part of a number of genetic syndromes associated with endocrine abnormalities, including hyperparathyroidism and pheochromocytoma (such as multiple endocrine neoplasia [MEN] 2 syndrome).1Anaplastic thyroid cancer (ATC) is uncommon, and is believed to develop from existing papillary or follicular carcinomas.1 Anaplastic thyroid cancer is one of the most aggressive and lethal of all solid malignancies. In most series, 3-year survival rates were less than 10%.3 Thyroid lymphoma is a rare disease that usually arises in the setting of pre-existing chronic lymphocytic thyroiditis (Hashimotos thyroiditis).2

References1. Detailed guide: thyroid cancer. American Cancer Society Web site. Available at: http://www.cancer.org/docroot/CRI/CRI_2_3x.asp?dt=43. Accessed December 10, 2003.2. Braverman LE, Utiger RD, eds. Werner & Ingbars The Thyroid: A Fundamental and Clinical Text. 8th ed. Philadelphia, Pa: Lippincott, Williams & Wilkins; 2000.3. Types of thyroid cancer. Virginia Masen Medical Center Web site. Available at: http://www.vmmc.org/dbCancer/sec180604.htm. Accessed December 10, 2003.

Papillary Thyroid CancerMost common typeMakes up about 80% of all thyroid carcinomas in the United StatesFemales outnumber males 3:1Highest incidence in women in midlife

Detailed guide: thyroid cancer. American Cancer Society Web site. Available at: http://www.cancer.org/docroot/CRI/CRI_2_3x.asp?dt=43. Accessed December 10, 2003.Thyroid Disease Manager Web site. Available at: http://www.thyroidmanager.org. Accessed December 10, 2003.

73Papillary Thyroid Cancer. Papillary thyroid cancer is the most common type of thyroid cancer and accounts for approximately 80% to 85% of all diagnosed thyroid cancers in the United States.1Papillary thyroid cancer has a 3-fold higher incidence in women than in men, and has a peak incidence in the third and fourth decades of life.2Approximately two thirds of PTC is found to have follicular elements and is often classified histologically as a follicular variant of papillary thyroid carcinoma.2

References1. Detailed guide: thyroid cancer. American Cancer Society Web site. Available at: http://www.cancer.org/docroot/CRI/CRI_2_3x.asp?dt=43. Accessed December 10, 2003.2. Thyroid Disease Manager Web site. Available at: http://www.thyroidmanager.org. Accessed December 10, 2003.

Papillary Thyroid CancerCharacteristicsUnencapsulated tumor nodule with ill-defined marginsTumor typically firm and solidMay present as nodal enlargementCommonly metastasizes to neck and mediastinal lymph nodes40% to 60% in adults and 90% in children